Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης

Correlation of Cardiovascular Risk Factors and Biomarkers With Platelet Reactivity in Coronary Artery Disease

Background: Low response to aspirin, aspirin resistance, and high platelet reactivity on aspirin treatment are similar names for lack of response to block arachidonic acid–induced aggregation with aspirin therapy and have an important role in the evolution of coronary artery disease (CAD) with thromboembolic events. Study Question: Was to evaluate the correlation between cardiovascular risk factors, biomarkers, and low response to aspirin in patients (pts) with CAD. Study Design: Four hundred pts with CAD were divided into 8 groups of study, consistent with the type of CAD and low response to aspirin. Cardiovascular risk factors and biomarkers—including some of high platelet reactivity, endothelial dysfunction, hypercoagulability, and oxidative stress—were evaluated in correlation with low response to aspirin, defined as on treatment aspirin test (ASPItest) >30U by multiple electrode platelet aggregometry. Results: In patients with CAD, low response to aspirin was significantly correlated with age older than 65 years, smoking, presence of diabetes mellitus, body mass index >25, hypertension, previous aspirin treatment, low response to clopidogrel, high mean platelets volume and von Willebrand factor activity, low flow-mediated vasodilation, and total antioxidant status (P < 0.01). In unstable angina patients, low response to aspirin was significantly correlated with male sex (P < 0.03). Incidence of other hypercoagulability biomarkers—S Protein, C Protein, Antithrombin III, and V Factor Leiden resistance to activated protein C—was low and not correlated with low response to aspirin. Conclusions: In CAD, low response to aspirin was significantly correlated with age older than 65 years, smoking, presence of diabetes mellitus, body mass index I >25, hypertension, previous aspirin treatment, and only in unstable angina with male sex. Low response to aspirin was also statistically associated with low response to clopidogrel, high mean platelets volume, high von Willebrand factor activity, low flow-mediated vasodilation, and low total antioxidant status values.

Intravenous Immunoglobulin Therapy in Refractory Autoimmune Dysautonomias: A Retrospective Analysis of 38 Patients

Background: Intravenous immunoglobulin (IVIG) has recognized efficacy in autoimmune peripheral nerve disorders, but there has been limited study of the use of IVIG in autoimmune dysautonomias. Study Question: To determine the efficacy and safety of IVIG in patients with disabling, refractory autoimmune dysautonomias, including patients with postural tachycardia syndrome and gastrointestinal dysmotility. Study Design: Patients with one or more autonomic disorder(s) and persistent serological evidence for autoimmunity who were unable to work or attend school despite usual treatments for dysautonomia were treated with IVIG for at least 3 months at a dose of at least 1 gm/kg monthly. Measures and Outcomes: Outcome measures included the composite autonomic symptom scale 31 survey and a functional ability score. Results: There were 38 patients, 84% female and mean age of 28.4 years. Of patients, 83.5% improved on IVIG as defined by at least 20% improvement in the composite autonomic symptom scale 31 and/or functional ability score. The mean pretreatment functional ability score was 21% (mostly bedridden), which improved to a mean of 74% (nearing able to return to work/school) for responsive patients after at least 1 year of IVIG. The mean time to the first sign of response was 5.3 weeks. There were no serious adverse events. The Mayo autoimmune dysautonomia panel antibodies and traditional Sjögren antibodies were present in only 13% and 8% of patients, respectively, but antiphospholipid antibodies and novel Sjögren antibodies were present in 76% and 42% of patients, respectively. Conclusions: There is increasing evidence that IVIG is safe and effective in a subset of patients with autonomic disorders and evidence for autoimmunity. A 4-month IVIG trial should be considered in severely affected patients who are refractory to lifestyle and pharmacological therapies. Antiphospholipid antibodies and novel Sjögren antibodies are often present in these patients and correlate with a high response rate to IVIG.

Effects of “Essential AD2” Supplement on Blood Acetaldehyde Levels in Individuals Who Have Aldehyde Dehydrogenase (ALDH2) Deficiency

Background: It is estimated that 1 billion people in the world have a point mutation in the gene encoding the aldehyde dehydrogenase 2 (ALDH2) enzyme, the primary enzyme responsible for the metabolism of acetaldehyde. The presence of this mutation is called ALDH2 deficiency. Because of limited ability to metabolize acetaldehyde, individuals with ALDH2 deficiency experience elevated levels of blood acetaldehyde after exposure to various common sources such as recreational alcohol. Because of higher levels of acetaldehyde, individuals with ALDH2 deficiency are at higher risk for numerous diseases, including liver cirrhosis, esophageal and gastric cancer, osteoporosis, and Alzheimer disease. Study Question: The present trial was designed to study the effectiveness, safety, and tolerability of a nutritional supplement (Essential AD2). Measures and Outcomes: The primary outcome was change in acetaldehyde levels in the blood after exposure to alcohol in individuals with ALDH2 deficiency before and after the use of study nutritional supplement. Study Design: This was a 28-day open-label trial, comparing initial acetaldehyde levels after alcohol ingestion to levels after 28 days of a nutritional supplement (Essential AD2). The study consisted of 12 subjects genotyped to be heterozygous for the ALDH2 gene mutation. Results and Conclusions: ALDH2 deficient subjects showed a significant decrease in average blood acetaldehyde level 20 minutes after alcohol consumption (from 0.91 mg/dL to 0.71 mg/dL, P value = 0.02) after receiving 28 days of the nutritional supplement. Acetaldehyde levels taken at 10 minutes and 40 minutes also showed a decrease, although they were not statistically significant. In addition, safety tests looking at liver function tests showed a decrease in aspartate transaminase and alanine transaminase liver proteins from 27.3 to 15.2 and 20.9 to 13.2, respectively, over the 28 days. The treatment was well tolerated and no significant side effects were noted.

Background: There is no clear consensus on the relationship between tenofovir (TDF) and fracture risk because the studies published so far present contradictory findings. Study Question: Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of fracture risk during TDF exposure in patients infected with HIV. Methods: Herein, we analyze all the cases of fractures suspected to be related to TDF recorded in EudraVigilance between 2001 and November 10, 2016. A case/noncase method was used to assess the association between fractures and TDF, calculating proportional reporting ratios (PRRs) and their 95% confidence intervals (CIs) as a measure of disproportionality. According to the Medical Dictionary for Regulatory Activities (MedDRA) terminology, osteoporotic fractures are included in High Level Group Term (HLGT) “Fractures” and traumatic fractures in HLGT “Bone and joint injuries,” so, we selected cases included in both HLGTs. The noncases used as controls were all the remaining adverse drug reaction reports recorded in EudraVigilance during the same period. Results: There were 68,113 cases of fractures in the 4,776,472 reports recorded in EudraVigilance during the study period. TDF was involved in 181 cases. The median latency period until the appearance of fracture was 995 days. TDF was present as the only suspect drug in 140 cases. The PRR of TDF and fractures was 1.11 (95% CI, 0.96–1.28). Nevertheless, disproportionality was observed for some types of fractures: osteoporotic fractures (PRR 17.24; 95% CI, 9.90–30.01), bone fissure (PRR 16.60; 95% CI, 6.11–45.10), and pathological fracture (PRR 4.40; 95% CI, 2.77–7.00). Conclusions: Our findings do not show a disproportionality for fractures in patients treated with TDF, although disproportionality was found for some types of fractures, mainly osteoporotic fractures.

Aspirin Resistance: Cardiovascular Risk Game Changer

Background: Aspirin (ASA) is the most used medication on the globe. ASA is a primary pillar of the secondary prevention of cardiovascular atherothromboembolic events. However, a fraction of the population does not respond to ASA as expected in a unique phenomenon called ASA resistance. Multiple mechanisms were described and studied in the literature to explain this phenomenon. Area of Uncertainty: ASA resistance is an interesting phenomenon that is worth studying and reviewing. Mechanisms behind this resistance are various and although the rarity of some, it is crucial for the modern health provider to be aware of such phenomenon and its possible explanations to provide more efficient preventive cardiology practice. Our study aimed to review and conclude the evidence behind ASA resistance and its implication on the cardiovascular health. Data Sources: We searched databases like PubMed, EMBASE, Ovid by midline, and Google Scholar for published articles and abstracts. Results: Our systemic search revealed more than 100 articles in relation to ASA resistance. We selected 40 articles, which were relevant for this review. Various mechanisms were described in the literature, with few of them very well documented and understood. Main mechanisms include medication nonadherence, interaction with proton pump inhibitors, esterase-mediated ASA inactivation, post-coronary artery bypass grafting (CABG) MRP-4–mediated ASA consumption, cyclooxygenase-1 (COX-1) polymorphisms, high platelet turnover–associated regeneration of platelet COX-1, and the documented platelet ability of de novo COX-1 synthesis in response to thrombin and fibrinogen. Conclusion: Multiple mechanisms of ASA resistance were described in the literature. Awareness of such interaction is important for medical practitioners. Bottom line, further studies and reviews are needed to further study this phenomenon and its implication on the cardiovascular health and hence reaching a valid evidence-based conclusion that might change the practice and improve the patient preventive health care.

Sirolimus for Recurrent Giant Cell Myocarditis After Heart Transplantation: A Unique Therapeutic Strategy

Clinical Features: Giant cell myocarditis (GCM) is a rare and a rapidly progressive disorder with fatal outcomes such that patients often require heart transplantation. We present a case of recurrent GCM in a transplanted patient with a history of Crohn disease requiring a novel therapeutic approach. Therapeutic Challenge: After the orthotopic heart transplantation, GCM recurred on aggressive immunosuppression over the months, which included corticosteroids, basiliximab, tacrolimus, antithymocyte globulin, and rituximab. Although combination immunosuppressive therapy containing cyclosporine and 2–4 additional drugs including corticosteroids, azathioprine, mycophenolate mofetil, muromonab, gammaglobulin, or methotrexate have shown to prolong the transplant-free survival by keeping the disease under control, its role in preventing and treating recurrence posttransplantation is unclear. Solution: We added sirolimus, a macrolide antibiotic, with properties of T- and B-lymphocyte proliferation inhibition on the above immunosuppressive treatment postrecurrence of GCM. After sirolimus initiation and continuation, the patient has remained disease free.

Oral Care and Ventilator-Associated Pneumonia